体外皮肤刺激模型的生物标志研究进展

©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[](30670541),(2008IK257)[](1971-),,,E2mail:[e-mail],(,510623),,,,,,,;;R394134A167127856(2010)0320064205ProgressonBiomarkersofSkinIrritationModelsinvitroCHENGShu2jun,PANFang(FoodLabofGuangdongEntry2ExitInspectionandQuarantineTechnologyCenter,GuangZhou510623,China)AbstractSkinirritanttestwastheroutinelyconductedforhumanhealthyrelatedproducthazardassessment.Traditionalskinirritancytestingusedlabanimals,costly,time2consumingandsufferingfromstress.Recentyears,diversealternativemodelsforskinirritancyhavebeendevelopedandapplied.Theeffectsinvivowerepredictedinvitrotestingbyquantitativemeasuredcellviabilityandbiomarkersformetabolismdisturbing.Thebiomarkersforskinirritancyincludedviability,inflammationcytokines,enzymes,morphology,etc.Newspeciallybiomarkerswillbedevelopedandvalidatedunderbiotechniqueimprovement.KeywordsBiomarker;Skinirritancy;Alternativemodel,,()/[1-5],,,DNA1,,,(),()[3-7]1[1],,©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[2],,[1],,,K6/K16,,(IV),,,,[3],1Tab.1InvitromodelforskinirritationtestAlternativemodelMeasuredendpointsIrritancyrangeChemicalclassEpiSkinEpiSkinTMmodelMTT,IL21aViabilitybyMTT,IL21areleaseIrritantsandnon2irritantsEpiDermEpiDermTMmodelMTT,IL21aViabilitybyMTT,IL21areleaseIrritantsandnon2irritantsSkinEthicTMRHESkinEthicTMmodelMTT,,IL21aIL28ViabilitybyMTT,tissuehistology,IL21aandIL28release,Irritantsandnon2irritants,IrritantsandsensitizingPrediskinMTT,ViabilitybyMTT,tissuehistologyIrritantsandnon2irritantsMouseskinintegrityfunctiontest,Trans2epidermalwaterloss,electricalresistanceIrritantsandnon2irritantsCulturedkeratinocytesIL21a,TNF2aCytokinesIL21aandTNF2arelease,Lackstratumcorneum3T3Coculturedhumankeratinocytesand3T3cells,,ViabilitybyNRuptake,morphology,expressionandreleaseofcytokines,Lackstratumcorneum,HighsensitivityAltskinTMAltskinTMmodelMTT,,IL/8IL21aViabilitybyMTT,tissuehistology,IL/8IL21aratio,Irritants,non2irritantsandsensitivity:;;Note:Diversegroupofchemicalswithvaryingphysicochemicalproperties;Avoidpoorlywater2solublechemicals;Notdefinedduetolowpredictivity2MTT,211(MTT)(LDH)[4],MTT,(1)[1-6],2121(IL21)IL21IL21(37103),5620103203ChinJCompMed,March2010,Vol.201No.3©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(AP21)IL21IL21?PonecSLS,IL21,IL21SLS[5]IL21[6],,IL21IL21IL26IL28ECVAMIL21MTT,MTT50%,(R38);MTT50%,IL2150pg/mL,(R38),(NI)IL21(IL21r),IL21IL21rIL21IL21,IL21IL21rBernhoferIL21r[6]IL21rIL21[8]2136(IL26)IL26(26103),BIL26,IL26[6],IL26IL26,2148(IL28)IL28C2X2C,,IL21IL21IFN2TNF2IL28IL28,IL28BernhoferIL28,()IL28,,IL28,[6]IL28IL21[9]21510(IL210)IL210,IL210,,IL210,,IL210[10]216(TNF2)TNF217103,TNF2,,IL21TNF2BernhoferSDS,16hTNF2mRNA,TNF2[6],TNF2[11]217(arachidonicacid)6620103203ChinJCompMed,March2010,Vol.201No.3©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(PLA2,PLC),,,B4152PLA2,MAPK,2PGEE2(PGE2),PGE2PGE2,EpiDermPGE2,Skinethic[12]218,,,30min,C,PLA2,SLS,,3,,,,,,,311,,,CCL227CCR10CLA+TSDS(SKALP)/,TNF24SKALP/[10]SKALPSKALP,SKALP,(MPO)deJongh,SDS27,,MPO,MPOSDSCCL11CXCL10,IL21aBFGE,IL21RA,CCL5IL21RA/IL21a[13]SDS,CCL20CCL27CXCL18,,,IL21aTNF2a,CCL20CXCL8,CCL27IL21aTNF2a312FletcherSLSEPIDERM15min24h,CDNA,DNA[14]Borlon[15],24016,BoxmanSLS,7,27[16]Gibbs[17],CCL27,CCL277620103203ChinJCompMed,March2010,Vol.201No.3©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[12]313,,,()()[2]3Mel2CaM,;NGFgp145,,,,;,;,,,,,,,,:[1]CoquetteA,BernaN,VandenboschA,etal.Analysisofinterleukin21alpha(IL21alpha)andinterleukin28(IL28)expressionandreleaseininvitroreconstructedhumanepidermisforthepredictionofinvivoskinirritationand/orsensitization[J].ToxicolinVitro,2005,17(3),311-321.[2]BernardFX,PedrettiN,RosdyM,etal.Comparisonofgeneexpressionprofilesinhumankeratinocytemono2layercultures,reconstitutedepidermisandnormalhumanskin;transcriptionaleffectsofretinoidtreatmentsinreconstitutedhumanepidermis[J].ExpDermatol,2002,11:59-74.[3]Schafer2KortingM,BockU,DiembeckW,etal.Theuseofreconstructedhumanepidermisforskinabsorptiontesting:resultsofthevalidationstudy[J].ALTA,2008,36(2),161-187.[4]VandeSandtJ,RoguetR,CohenC,etal.Theuseofhumankeratinocytesandhumanskinmodelsforpredictingskinirritation[J].ATLA,1999,27:723-743.[5]PonecM,KempenaarJ.Theuseofhumanskinrecombinantsasaninvitromodelfortestingtheirritationpotentialofcutaneousirritants[J].SkinPharmacol,1995,8:49-59.[6]BernhoferLP,SeibergM,MartinKM.Theinfluenceoftheresponseofskinequivalentssystemstotopicallyappliedconsumerproductsbyepithelialmesenchymalinteraction[J].ToxicolVitro,1999,13:219-229.[7],,,.Inspectskin[J].(),2009,30(2):132-135.[8]PerkinsMA,OsterhuesMA,FarageMA,etal.Anoninvasivemethodtoassessskini